Effects of Adiponectin on Proliferation of Airway Smooth Muscle Cells and Activation of Adenosine Monophosphate-Activated Protein Kinase_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

GUO Maoqing , ZHU Shuyang

Department of Respiratory Medcine, Affliated Hospital of Xuzhou Medical College. Xuzhou, Jiangsu,221002, ChinaCorrespordiny Author: ZHU Shu-yang, E-mail: xiaoqing8402@ 163. com;

Corresponding author：

Keywords：

Adiponectin; Airway smooth muscle cell; Proliferation; Adenosine monophosphate-activated kinase

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Objective To investigate the effect of adiponectin on proliferation of airway smooth muscle cells( ASMCs) , and explore its possible mechanism. Methods ASMCs were derived fromrat airway tissue and were cultured in vitro. RT-PCR was used to verify the expression of adiponectin receptors on ASMCs. Then ASMCs were treated with adiponectin at different concentrations( 5, 10, 20, 40, 80 μg/mL) for different periods of time( 1, 12, 24, 48, 72 hours) , respectively. The absorbsence ratios of adiponectin at different concentrations were determined by MTT assay. The adenosine monophosphate-activated protein kinase( AMPK) and phosphorylated AMPK( pho-AMPK) in ASMCs were quantified by Western blot after being treated with adiponectin at different concentrations ( 5, 10, 20, 40 μg/mL) for 48 hours. Results
The inhibition of adiponectin on ASMCs was showed in dose-dependent manner( r = 0. 324, P lt; 0. 01) and time-dependent manner( r = 0. 607, P lt; 0. 05) . Western blot indicated that the expression of pho-AMPK increased with the increased concentrations of adiponectin( r =0. 607, P lt; 0. 01) . The ratio of pho-AMPK/AMPK were ( 27. 66 ±1. 03) % , ( 31. 91 ±0. 86 ) %, ( 75. 52 ±2. 67) % , and ( 84. 50 ±1. 05) % ,respectively, with significant differences between each concentrations of adiponectin( P lt; 0. 05) . There was no expression of pho-AMPK in the control group. Conclusion Adiponectin can significantly inhibit ASMCs’proliferation by activating AMPK.

Citation： GUO Maoqing,ZHU Shuyang. Effects of Adiponectin on Proliferation of Airway Smooth Muscle Cells and Activation of Adenosine Monophosphate-Activated Protein Kinase. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(3): 264-267. doi: Copy

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9.	Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun, 2006,345: 271-279.
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11.	Konturek PC, Burnat G, Rau T, et al. Effect of adiponectin and ghrelin on apoptosis of barrett adenocarcinoma cell line. Dig Dis Sci, 2008, 53: 597 -605.
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13.	Nagata D, Takeda R, Sata M, et al. AMP-activated protein kinase inhibits angiotensin II-stimulated vascular smooth muscle cell proliferation. Circulation, 2004, 110 : 444-451 .
14.	Ratnovsky A, Mellema M, An SS, et al. Airway smooth muscle proliferation and mechanics: effects of AMP kinase agonists. Mol Cell Biomech, 2007 , 4: 143-157.
15.	Motoshima H, Goldstein BJ, Igata M, et al. AMPK and cell proliferation-AMPK as a therapeutic target for atherosclerosis and cancer. J Physiol, 2006, 574( Pt 1) : 63-71.

1. Woodruff PG, Dolganov GM, Ferrando RE, et al. Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression. Am J Respir Crit Care Med, 2004 , 169 :1001-1006.
2. 蔡绍曦, 赵海金. 气道重塑成为哮喘新的治疗靶点还有多远?中国呼吸与危重监护杂志, 2006, 5: 404 -407.
3. Taylor B, Mannino D, Brown C, et al. Body mass index and asthma severity in the National Asthma Survey. Thorax, 2008, 63: 14 -20 .
4. Shore SA. Obesity and asthma: implications for treatment. Curr Opin PulmMed, 2007 , 13 : 56-62.
5. Ouchi N, Kihara S, Funahashi T, et al. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol, 2003, 14: 561-566.
6. James A. Airway remodeling in asthma. Curr Opin PulmMed, 2005 ,11: 1-6.
7. Ammit AJ, Panettieri RA Jr. Airway smooth muscle cell hyperplasia:a therapeutic target in airway remodeling in asthma. Prog Cell Cycle Res, 2003, 5 : 49-57.
8. Shore SA, Fredberg JJ. Obesity, smooth muscle, and airway hyperresponsiveness. J Allergy Clin Immunol, 2005 , 115: 925-927 .
9. Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun, 2006,345: 271-279.
10. Cong L, Gasser J, Zhao J, et al. Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells,HEC-1-A and RL95-2. Endocr Relat Cancer, 2007, 14; 713-720.
11. Konturek PC, Burnat G, Rau T, et al. Effect of adiponectin and ghrelin on apoptosis of barrett adenocarcinoma cell line. Dig Dis Sci, 2008, 53: 597 -605.
12. Igata M, Motoshima H, Tsuruzoe K, et al. Adenosine monophosphateactivated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res, 2005, 97: 837 -844.
13. Nagata D, Takeda R, Sata M, et al. AMP-activated protein kinase inhibits angiotensin II-stimulated vascular smooth muscle cell proliferation. Circulation, 2004, 110 : 444-451 .
14. Ratnovsky A, Mellema M, An SS, et al. Airway smooth muscle proliferation and mechanics: effects of AMP kinase agonists. Mol Cell Biomech, 2007 , 4: 143-157.
15. Motoshima H, Goldstein BJ, Igata M, et al. AMPK and cell proliferation-AMPK as a therapeutic target for atherosclerosis and cancer. J Physiol, 2006, 574( Pt 1) : 63-71.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of Adiponectin on Proliferation of Airway Smooth Muscle Cells and Activation of Adenosine Monophosphate-Activated Protein Kinase

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